三阳清解液乙状结肠滴注对内毒素诱导大鼠发热模型解热机制的研究
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摘要
目的:探讨三阳清解液乙状结肠滴注对大鼠内毒素(LPS)诱导发热模型的退热作用机制。方法 :将40只大鼠随机分为4组,空白组、模型组、对乙酰氨基酚组、三阳清解液组,除空白组外,其他各组腹腔注射LPS(20μg/kg)建立大鼠发热模型,观察用药后每小时的体温变化,连续监测6 h,留取下丘脑和血清标本,用酶联免疫吸附试验(ELISA)测定各组大鼠下丘脑环磷酸腺苷(cAMP)、前列腺素E_2(PGE_2)含量和血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、PGE_2的含量。结果:LPS造模后大鼠呈典型的双峰热;与空白组比较,模型组大鼠体温明显上升(P<0.05);三阳清解液能明显降低发热大鼠体温,与模型组对比具有明显差异(P<0.05);与对乙酰氨基酚组在给药1、2 h退热效果比较,差异有统计学意义(P<0.05),而在给药4、5、6 h比较,差异无统计学意义(P<0.05);ELISA结果显示:与空白组比较,模型组大鼠下丘脑cAMP、PGE_2及血清IL-1β、TNF-α、PGE_2含量显著升高(P<0.01);与模型组比较,对乙酰氨基酚及三阳清解液组大鼠下丘脑cAMP、PGE_2及血清IL-1β、TNF-α、PGE_2含量显著下降(P<0.05),其中三阳清解液组下丘脑PGE_2及血清IL-1β、PGE_2与对乙酰氨基酚组无显著差异(P>0.05)。结论 :三阳清解液对LPS诱导的发热大鼠模型有良好的解热作用,其机制可能是通过下调大鼠下丘脑cAMP、PGE_2水平,从而抑制血清IL-1β、TNF-α、PGE_2的表达有关。
Objective: To explore the antipyretic mechanism of Sanyang Qingjie Liquid through sigmoid instillation in rat model with fever induced by lipopolysaccharide(LPS). Methods: 40 rats were randomly divided into the blank group, the model group, the Acetaminophen group, and the group of Sanyang Qingjie Liquid, with 10 rats in each group. The rat model of fever was established by intraperitoneal injection of LPS(20 μg/kg). Body temperature was observed every hour after the medication for continuous 6 hours. Afterwards, the samples of hypothalamus were collected. The hypothalamus contents of cAMP and PGE_2, as well as the serum levels of IL-1β, TNF-α, and PGE_2 were determined by ELISA method. Results: The rats presented with a double peaked fever after modeling. The body temperature was significantly heightened in the model group compared to that in the blank group(P<0.05); it was greatly lowered in Sanyang Qingjie Liquid group compared to that in the model group(P<0.05). There was significant difference in body temperature 1 h and 2 h after the medication between the Sanyang Qingjie Liquid group and the Acetaminophen group(P<0.05); however, no differences were seen 4 h, 5 h, and 6 h after the medication between the two groups(P>0.05). The results of ELISA showed that the levels of cAMP and PGE_2 in hypothalamus and IL-1β, TNF-α, PGE_2 in serum were significantly increased in the model group compared to those in the blank group(P<0.05); they were significantly decreased in the two medication groups compared to those in the model group(P<0.05); there was no significant difference in hypothalamus content of PGE_2 and in serum levels of IL-1β and PGE_2 between the two medication groups(P>0.05). Conclusion: Sanyang Qingjie Liquid has a nice antipyretic effect in rat model of LPS-induced fever. Its mechanism may be related to down-regulating the levels of cAMP and PGE_2 in hypothalamus to inhibit the serum expressions of IL-1β, TNF-α and PGE_2.
Objective: To explore the antipyretic mechanism of Sanyang Qingjie Liquid through sigmoid instillation in rat model with fever induced by lipopolysaccharide(LPS). Methods: 40 rats were randomly divided into the blank group, the model group, the Acetaminophen group, and the group of Sanyang Qingjie Liquid, with 10 rats in each group. The rat model of fever was established by intraperitoneal injection of LPS(20 μg/kg). Body temperature was observed every hour after the medication for continuous 6 hours. Afterwards, the samples of hypothalamus were collected. The hypothalamus contents of cAMP and PGE_2, as well as the serum levels of IL-1β, TNF-α, and PGE_2 were determined by ELISA method. Results: The rats presented with a double peaked fever after modeling. The body temperature was significantly heightened in the model group compared to that in the blank group(P<0.05); it was greatly lowered in Sanyang Qingjie Liquid group compared to that in the model group(P<0.05). There was significant difference in body temperature 1 h and 2 h after the medication between the Sanyang Qingjie Liquid group and the Acetaminophen group(P<0.05); however, no differences were seen 4 h, 5 h, and 6 h after the medication between the two groups(P>0.05). The results of ELISA showed that the levels of cAMP and PGE_2 in hypothalamus and IL-1β, TNF-α, PGE_2 in serum were significantly increased in the model group compared to those in the blank group(P<0.05); they were significantly decreased in the two medication groups compared to those in the model group(P<0.05); there was no significant difference in hypothalamus content of PGE_2 and in serum levels of IL-1β and PGE_2 between the two medication groups(P>0.05). Conclusion: Sanyang Qingjie Liquid has a nice antipyretic effect in rat model of LPS-induced fever. Its mechanism may be related to down-regulating the levels of cAMP and PGE_2 in hypothalamus to inhibit the serum expressions of IL-1β, TNF-α and PGE_2.
引文
[1] 王晓燕,汤瑞莲,刘宝琴,等. 三阳清解液乙状结肠滴注对内毒素诱导发热模型大鼠体温及血清IL-6、MIP-1含量的影响[J].中国中医急症,2018,27(1):82-85.
[2] 王晓燕,马丙祥,陈宪忠,等.三阳清解煎剂直肠滴注治疗小儿外感发热临床研究[J].时珍国医国药,2007,18(4):838-840.
[3] 徐向东,赵珠祥,赵海霞.清营汤对内毒素致热家兔的作用及其机制[J].中国实验方剂学杂志,2012,18(24):220-222.
[4] Kong XY,Wan HY,Su XH,et al.Rheum pal-matum L.and Coptis chinensis Franch. exert antipyretic effecton yeast-induced pyrexia rats involving regulation of TRPV1 and TRPM8 expression[J].J Ethnopharmacol,2014,159(3):160-168.
[5] 吴佳霖,吕邵娃,孙亚丽,等.白虎汤对不同大鼠发热模型解热机制的研究[J].中南药学,2018,16(14):492-495.
[6] 巴图德力根,韩志强,娜日苏,等.达如奇颗粒解热作用及其对下丘脑PGE2和血清TNF-α含量的影响[J].中药药理与临床,2013,29(6):113-115.
[7] 韩庆荣,刘明云,张永科,等.一笑退热散对大鼠内毒素诱导发热模型退热机制的实验研究[J].儿科药学杂志,2015,21(2):1-4.
[8] 周晓英,李世兵,张林,等.针刺曲池与合谷对发热大鼠下丘脑前列腺素E2的影响[J].针灸临床杂志,2015,31(11):64-67.
[9] 袁岸,李燕,罗林,等.连翘提取物对酵母和脂多糖所致大鼠发热模型的影响研究[J].辽宁中医杂志,2017,44(2):405.
[10] 党珏,袁岸,罗林,等.连翘提取物和连翘挥发油对酵母致热大鼠的解热机制研究[J].天然产物研究与开发,2017,29(9):1542-1545.
[11] 王雪峰,韩雪梅,任存霞.王氏连朴饮加滑石、黄芩;茵达日-4味汤对温病湿热模型、炎性反应因子IL-1β、IL-6、TNF-α的影响[J].世界中医药,2014,9(11):1524-1527.
[12] 万宇翔,郑子安,白辰,等.银莱汤对发热大鼠血清IL-1β、TNF-α、IL-6含量的影响[J].湖南中医药大学学报,2017,37(11):1184-1187.
[13] 聂坚,胡文敏,李刚,等.香芩解热颗粒对酵母致热大鼠的解热作用[J].中华中医药杂志,2017,32(10):4692-4695.
[14] Bibek Khanal,施蓓,Puja Paudel,等.脑室给予不同剂量的Capsazepine对LPS致大鼠发热过程的影响[J].中国药理学通报,2015,31(1):35-38.
[15] 韩玲,赵一粒.热必清颗粒对发热模型大鼠体温及血清IL-1β影响的实验研究[J].湖南中医杂志,2016,32(10):174-189.
[16] 曹峰,唐阿梅.不同柴胡剂量小柴胡汤对 LPS 诱导发热大鼠模型体温及血清 IL-1β、IL-6、TNF-α的影响[J].世界科学技术-中医药现代化,2014,16(1):58-62.
[17] 刘进娜,谢鸣.补中益气汤及其不同配伍对脾虚发热模型的退热作用比较[J].中华中医药杂志,2014,29(6):1814-1818.
[18] Liu X,Tang YP,Liu R,et al.Antipyretic and anti-inflammatory activities of Thais luteostoma extracts and underlying mechanisms[J].Chin J Nat Med,2015,13(3):192-198.
[2] 王晓燕,马丙祥,陈宪忠,等.三阳清解煎剂直肠滴注治疗小儿外感发热临床研究[J].时珍国医国药,2007,18(4):838-840.
[3] 徐向东,赵珠祥,赵海霞.清营汤对内毒素致热家兔的作用及其机制[J].中国实验方剂学杂志,2012,18(24):220-222.
[4] Kong XY,Wan HY,Su XH,et al.Rheum pal-matum L.and Coptis chinensis Franch. exert antipyretic effecton yeast-induced pyrexia rats involving regulation of TRPV1 and TRPM8 expression[J].J Ethnopharmacol,2014,159(3):160-168.
[5] 吴佳霖,吕邵娃,孙亚丽,等.白虎汤对不同大鼠发热模型解热机制的研究[J].中南药学,2018,16(14):492-495.
[6] 巴图德力根,韩志强,娜日苏,等.达如奇颗粒解热作用及其对下丘脑PGE2和血清TNF-α含量的影响[J].中药药理与临床,2013,29(6):113-115.
[7] 韩庆荣,刘明云,张永科,等.一笑退热散对大鼠内毒素诱导发热模型退热机制的实验研究[J].儿科药学杂志,2015,21(2):1-4.
[8] 周晓英,李世兵,张林,等.针刺曲池与合谷对发热大鼠下丘脑前列腺素E2的影响[J].针灸临床杂志,2015,31(11):64-67.
[9] 袁岸,李燕,罗林,等.连翘提取物对酵母和脂多糖所致大鼠发热模型的影响研究[J].辽宁中医杂志,2017,44(2):405.
[10] 党珏,袁岸,罗林,等.连翘提取物和连翘挥发油对酵母致热大鼠的解热机制研究[J].天然产物研究与开发,2017,29(9):1542-1545.
[11] 王雪峰,韩雪梅,任存霞.王氏连朴饮加滑石、黄芩;茵达日-4味汤对温病湿热模型、炎性反应因子IL-1β、IL-6、TNF-α的影响[J].世界中医药,2014,9(11):1524-1527.
[12] 万宇翔,郑子安,白辰,等.银莱汤对发热大鼠血清IL-1β、TNF-α、IL-6含量的影响[J].湖南中医药大学学报,2017,37(11):1184-1187.
[13] 聂坚,胡文敏,李刚,等.香芩解热颗粒对酵母致热大鼠的解热作用[J].中华中医药杂志,2017,32(10):4692-4695.
[14] Bibek Khanal,施蓓,Puja Paudel,等.脑室给予不同剂量的Capsazepine对LPS致大鼠发热过程的影响[J].中国药理学通报,2015,31(1):35-38.
[15] 韩玲,赵一粒.热必清颗粒对发热模型大鼠体温及血清IL-1β影响的实验研究[J].湖南中医杂志,2016,32(10):174-189.
[16] 曹峰,唐阿梅.不同柴胡剂量小柴胡汤对 LPS 诱导发热大鼠模型体温及血清 IL-1β、IL-6、TNF-α的影响[J].世界科学技术-中医药现代化,2014,16(1):58-62.
[17] 刘进娜,谢鸣.补中益气汤及其不同配伍对脾虚发热模型的退热作用比较[J].中华中医药杂志,2014,29(6):1814-1818.
[18] Liu X,Tang YP,Liu R,et al.Antipyretic and anti-inflammatory activities of Thais luteostoma extracts and underlying mechanisms[J].Chin J Nat Med,2015,13(3):192-198.